This proposal seeks support for a Research Scientist Award (KO5) to allow the candidate to continue full-time involvement in an comprehensive program of research in Psychiatric Genetics that he has been developing since 1983. This research program is supported by the following projects, on which the candidate is Principal Investigator: 1) the Irish High Density Schizophrenia Study, research involving a sample of over 270 schizophrenia multiplex families systematically ascertained from the entire island of Ireland, with the goal of detecting susceptibility loci for schizophrenia by linkage analysis; 2) the Roscommon Family Study, a large-sample, controlled, epidemiologic family study of schizophrenia and other major mental disorders based in the West of Ireland, the goal of which is to understand the familial determinants of schizophrenia and schizophrenia spectrum disorders; 3) the Female Twin-Family Virginia Twin Study, a sample of 1,033 longitudinally followed female-female twin pairs ascertained from the population-based Virginia Twin Registry and their parents, with the goal of understanding the role of genetic and environmental risk factors in the etiology of common psychiatric disorders and alcoholism in women and 4) the Male Virginia Twin Study, which is an on-going longitudinal study of 1,500 male-male and 1,300 male-female twin pairs, also from the Virginia Twin Registry. The goal of this final project is to clarify the genetic and environmental risk factors for the common psychiatric and substance use disorders in men and to understand the relationship between these factors and the risk factors that influence the vulnerability to these disorders in women. The candidate has been active in training Post-doctoral fellows and younger faculty for research careers in psychiatric genetics.